인체 간 microsome에서 pentoxifylline 대사체 M-1의 시험관내 대사

In Vitro Metabolism of Pentoxifylline Metabolite M-1 in Human Liver Microsomes

The metabolism and pharmacokinetics of M-1, which is metabolite of pentoxifylline, have been studied in human liver microsomes. Biphasic kinetics was observed from the Eadie-Hofstee plot for the formation of both metabolites of M-1. For the kinetics of pentoxifylline, mean values of Vmax1 and Vmax2 were 1.648 and 5.622nmol/min/mg protein, and the estimated values of Km1 and Km2 were 0.180 and 4.829mM, respectively. For M-3, mean values of Vmax1 and Vmax2 were 0.062 and 0.491nmol/min/mg protein, and estimated values of Km1 and Km2 were 0.025 and 1.216mM. The formations of pentoxifylline and M-3 from M-1 were identified by using several selective inhibitors of cytochrome P450 isoformes at 0.05-5mM concentratibn of M-1 in human liver microsomes. For the analysis of low (0.05mM) concentration of M-1, where the affinity was expected as low, indicated that CYP1A2 and CYP3A4 were major P450 isoforms responsible for pentoxifylline and M-3 formation. CYP3A4 and CYP2A6 appeared to be P450 isoforms responsible for M-3 formation at high (5mM) concentration of M-1.